A Study to Evaluate the Safety and Pharmacokinetics of Ataluren in Participants From ≥6 Months to <2 Years of Age With Nonsense Mutation Duchenne Muscular Dystrophy (nmDMD)

An Open-Label Study Evaluating the Safety and Pharmacokinetics of Ataluren in Children From ≥6 Months to <2 Years of Age With Nonsense Mutation Duchenne Muscular Dystrophy

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04336826

Enrollment

Registered

2020-04-07

Start date

2021-12-29

Completion date

2023-08-07

Last updated

2024-04-01

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Nonsene Mutation Duchenne Muscular Dystrophy

Brief summary

This study is designed to evaluate safety, tolerability, and pharmacokinetics (PK) in male children with nmDMD aged ≥6 months to \<2 years treated daily for 24 weeks with orally administered ataluren 10, 10, and 20 milligrams/kilogram (mg/kg) (morning, mid-day, and evening dose, respectively).

Detailed description

Participants who complete the 24-week treatment period in this study will be offered participation to a follow-up extension period for at least 52 weeks from the date of first administration of ataluren in this parent study.

Interventions

DRUGAtaluren

Ataluren will be administered as per the dose and schedule specified in the arm.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

MALE

Age

6 Months to 2 Years

Healthy volunteers

Inclusion criteria

* Body weight ≥7.5 kilograms (kg) * Diagnosis of duchenne muscular dystrophy (DMD) based on an elevated serum creatine kinase and genotypic evidence of dystrophinopathy. * Documentation of the presence of a nonsense mutation of the dystrophin gene as determined by gene sequencing prior to enrollment.

Exclusion criteria

* Participation in any drug or device investigation or whose sibling is currently participating in a blinded portion of another ataluren study or received an investigational drug within three months prior to the Screening Visit or who anticipate participating in any other drug or device clinical investigation or receiving any other investigational drug within the duration of this study. * Expectation of a major surgical procedure during the study period. * Known hypersensitivity to any of the ingredients or excipients of the study drug (polydextrose, polyethylene glycol 3350, poloxamer 407, mannitol 25C, crospovidone XL10, hydroxyethyl cellulose, vanilla, colloidal silica, or magnesium stearate). * Ongoing use of the following drugs: 1. Systemic aminoglycoside therapy and/or intravenous (IV) vancomycin. 2. Coumarin-based anticoagulants (for example, warfarin), phenytoin, tolbutamide, or paclitaxel. 3. Inducers of UGT1A9 (for example, rifampicin), or substrates of OAT1 or OAT3 (for example, ciprofloxacin, adefovir, oseltamivir, aciclovir, captopril, furosemide, bumetanide, valsartan, pravastatin, rosuvastatin, atorvastatin, pitavastatin).

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	Baseline up to Week 28	An adverse event (AE) was as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. Serious adverse event (SAE): an AE that met at least 1 of the following criteria: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, congenital anomaly/birth defect, important medical event. A TEAE was defined as an AE that occurred or worsened while on ataluren (on or after first dose of ataluren) up to 4 weeks after the last dose. A summary of all SAEs and Other AEs (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.

Secondary

Measure	Time frame
Area Under the Concentration-Time Curve From Time 0 to 24 Hours (AUC0-24) of Ataluren	Predose up to 12 hours postdose at Week 24
Area Under the Concentration-Time Curve Between Dosing Interval (AUC0-τ) of Ataluren	Predose up to 12 hours postdose at Week 24
Maximum Concentration (Cmax) of Ataluren	Predose up to 12 hours postdose at Week 24
Time to Maximum Plasma Concentration (Tmax) of Ataluren	Predose up to 12 hours postdose at Week 24
Trough Concentration (Ctrough) of Ataluren	Predose up to 12 hours postdose at Week 24

Countries

United States

Participant flow

Participants by arm

Arm	Count
Ataluren Participants received ataluren oral suspension 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening each day for up to 24 weeks.	6
Total	6

Baseline characteristics

Characteristic	Ataluren
Age, Continuous	1.153 years STANDARD_DEVIATION 0.4485
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	0 Participants
Race (NIH/OMB) Black or African American	0 Participants
Race (NIH/OMB) More than one race	1 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) White	5 Participants
Sex: Female, Male Female	0 Participants
Sex: Female, Male Male	6 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	0 / 6
other Total, other adverse events	5 / 6
serious Total, serious adverse events	0 / 6

Outcome results

Primary

Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

An adverse event (AE) was as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. Serious adverse event (SAE): an AE that met at least 1 of the following criteria: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, congenital anomaly/birth defect, important medical event. A TEAE was defined as an AE that occurred or worsened while on ataluren (on or after first dose of ataluren) up to 4 weeks after the last dose. A summary of all SAEs and Other AEs (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.

Time frame: Baseline up to Week 28

Population: Safety analysis set included all participants who received at least 1 dose of ataluren.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Ataluren	Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	5 Participants

Secondary